Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL
Authors: Darko Antic, Natasa Milic, Thomas Chatzikonstantinou, Lydia Scarfò, Vladimir Otasevic, Nina Rajovic, David Allsup, Alejandro Alonso Cabrero, Martin Andres, Monica Baile Gonzales, Antonella Capasso, Rosa Collado, Raul Cordoba, Carolina Cuéllar-García, Juan Gonzalo Correa, Lorenzo De Paoli, Maria Rosaria De Paolis, Giovanni Del Poeta, Maria Dimou, Michael Doubek, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Blanca Espinet, Lucia Farina, Angela Ferrari, Myriam Foglietta, Alberto Lopez-Garcia, José A. García-Marco, Rocío García-Serra, Massimo Gentile, Eva Gimeno, Maria Gomes da Silva, Odit Gutwein, Yervand K. Hakobyan, Yair Herishanu, José Ángel Hernández-Rivas, Tobias Herold, Gilad Itchaki, Ozren Jaksic, Ann Janssens, Olga B. Kalashnikova, Elżbieta Kalicińska, Arnon P. Kater, Sabina Kersting, Maya Koren-Michowitz, Jorge Labrador, Deepesh Lad, Luca Laurenti, Alberto Fresa, Mark-David Levin, Carlota Mayor Bastida, Lara Malerba, Roberto Marasca, Monia Marchetti, Juan Marquet, Biljana Mihaljevic, Ivana Milosevic, Fatima Mirás, Marta Morawska, Marina Motta, Talha Munir, Roberta Murru, Raquel Nunes, Jacopo Olivieri, Miguel Arturo Pavlovsky, Inga Piskunova, Viola Maria Popov, Francesca Maria Quaglia, Giulia Quaresmini, Gianluigi Reda, Gian Matteo Rigolin, Amit Shrestha, Martin Šimkovič, Svetlana Smirnova, Martin Špaček, Paolo Sportoletti, Oana Stanca, Niki Stavroyianni, Doreen Te Raa, Kristina Tomic, Sanne Tonino, Livio Trentin, Ellen Van Der Spek, Michel van Gelder, Marzia Varettoni, Andrea Visentin, Candida Vitale, Vojin Vukovic, Ewa Wasik-Szczepanek, Tomasz Wróbel, Lucrecia Yáñez San Segundo, Mohamed Yassin, Marta Coscia, Alessandro Rambaldi, Emili Montserrat, Robin Foà, Antonio Cuneo, Marc Carrier, Paolo Ghia, Kostas Stamatopoulos
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.